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Biomedical subjects

A Renaud

Publications and source records attributed to A Renaud.

63 records · Page 4Linked to original sources
PubMed1979

The interaction of trifluoroacetyl peptide chloromethyl ketones with porcine pancreatic elastase. Direct evidence for nonproductive enzyme.inhibitor complexes.

19F NMR investigations of the interactions between elastase and the reversible inhibitors CF3CO-Ala3, CF3CO-Lys-Ala2 and CF3CO-Ala4 show that these peptides have a single mode of binding to the enzyme. Furthermore the results indicate that the CF3CO-group experiences the same environment in all of the reversible complexes formed with these inhibitors. This agrees with the higher affinity of these peptides for the enzyme as compared to the corresponding acetylated inhibitors and confirms our earlier hypothesis of the existence of a specific binding site for the CF3CO-group on the enzyme. The interactions between elastase and the irreversible inhibitors CF3CO-Alan chloromethyl ketone (n = 2, 3, 4, 5) and CF3CO-Lys-Ala4 chloromethyl ketone have been investigated by enzymatic measurements and 19F NMR spectroscopy. The kinetic constants k2 and KI describing the irreversible inhibition are significantly lower for all the CF3CO-peptide chloromethyl ketones with exception of CF3CO-Ala2 chloromethyl ketone, than for the corresponding acetylated ones. Moreover, 19F NMR spectroscopy enabled us to demonstrate, for the tri- and tetrapeptide derivatives, the parallel formation of reversible nonproductive enzyme.inhibitor complexes. The spectroscopic properties of these complexes are completely different from those of the irreversible complexes but are similar to those observed with the reversible complexes described above. In the case of the pentapeptide chloromethyl ketones, fast hydrolysis of the peptide or fast inactivation of the enzyme does not allow observations to be made but does not exclude the existence of reversible nonproductive complexes. In fact, their existence is strongly suggested by the enzyme reaction rate measurements. The similarity of the properties of all the reversible complexes, their striking differences with those of all the irreversible complexes, as well as their mutual exclusivity, permit the conclusion that the CF3CO-group does not bind at one of the classical S subsites of elastase.

Amino Acid Chloromethyl Ketones↗
PubMed1979

Inhibition of human leukocyte elastase by acetyl and trifluoroacetyl oligopeptide chloromethyl ketones.

The action of human leukocyte elastase on a series of acetyl and trifluoroacetyl tri-, tetra-, and pentapeptide chloromethyl ketones has been investigated. Leukocyte and pancreatic elastases react quite differently with these irreversible inhibitors. For instance, leukocyte elastase has a much lower affinity for the compounds than pancreatic elastase. On the other hand, the inhibition rate constants of the two enzymes are not influenced in the same way by peptide chain elongation. The two elastases, however, share a common property: trifluoroacetyl tri- and tetraalanine chloromethyl ketones are more tightly bound but are less reactive than the corresponding acetylated inhibitors. This behavior is probably due to the formation of nonproductive complexes between the enzymes and the trifluoroacetylated inhibitors.

Humans↗
PubMedDate not supplied

Matrix proteinase inhibition by AE-941, a multifunctional antiangiogenic compound.

BACKGROUND: Matrix metalloproteinases (MMPs) play an important role in tissue remodeling under normal physiological and pathological conditions and are thus attractive targets for both diagnostic and therapeutic purposes. Here, we examined the effect of AE-941, an orally bioavailable standardized extract made of cartilage that shows significant antiangiogenic and antimetastatic properties in vivo, on the activity of various members of the MMP family. MATERIALS AND METHODS: The effect of AE-941 on the activity of MMPs was assessed by fluorimetric assays and by substrate gel zymography. RESULTS: AE-941 markedly inhibits the gelatinolytic activity of MMP-2 and to a lesser extent those of MMP-1, MMP-7, MMP-9 and MMP-13. AE-941 also inhibited the elastinolytic activities of MMP-2 and MMP-9 as well as MMP-12 (metalloelastase), porcine pancreatic elastase (PPE), and human leukocyte elastase (HLE). Western blot analysis revealed the presence within AE-941 of immunoreactive TIMP-like proteins, suggesting that these proteins may be at least partly responsible for the observed MMP inhibition. CONCLUSIONS: Taken together, these results demonstrate that AE-941 contains TIMP-like proteins that could be responsible for the specific inhibition of MMPs. Given the recent studies suggesting the presence within this compound of specific inhibitor(s) of endothelial cell proliferation, AE-941 appears as a pleotropic agent able to interfere with several biochemical steps leading to angiogenesis and to other physiopathological conditions. Since AE-941 is currently under Phase III clinical investigations, these findings are also of considerable importance for our understanding of its anticancer properties.

Angiogenesis Inhibitors↗
PubMedDate not supplied

[Growth rate and natural history of breast cancer].

Available data on growth rate of human breast cancers and their kinetic of cell proliferation were reviewed. Breast cancers are among those human cancers with the longest doubling time and the lowest labelling index, however the spread of the individual values is especially large. Analysis of the data indicate that half of the metastases began to grow more than about two years before the time when the primary tumor reached a clinically detectable size. The prognostic influence of the delay between the time when the tumor reached a clinically detectable size and the treatment is discussed. A correlation is observed between the growth rate of the primary tumors and the mean survival of the deceased patients. This is probably due to correlation between the growth rates of the primary and of the metastases. The growth rate of the primary seems to have little influence, if any, on the probability of metastatic dissemination per tumor cell. This probability varies widely among various clinical types of breast tumors and is probably correlated with other parameters such as the presence of an inflammatory reaction.

Breast Neoplasms↗
PubMedDate not supplied

[Epidemiological surveillance of infection by the human immunodeficiency virus (HIV) and of the acquired immunodeficiency syndrome (AIDS) in French Polynesia in 1991].

The authors make out a statement about HIV infection in French Polynesia at the date of 1991 December 31. 96 cases all together of seropositive and AIDS infected people were recorded. These patients are young generally (78 p.c. between 21 and 40 years old) sexually contaminated (72 out of 96) and live in Tahiti island (94 p.c.). Sex-ratio is 2.8 male/1 female. Among them, we noted 55 p.c. of Europeans, 38 p.c. of Polynesians and 7 p.c. of Asiatic people. Epidemiological monitoring of the infection was made easy because of a set of laws and possibilities of detection highly favourable. Progress of the infection is constant, with 20 new cases detected each year with a prevalence of 150 cases of AIDS per 1 million of inhabitants, French Polynesia could be classified as the 5th or 6th region of France as far as the importance of the disease. Clinical, biological and epidemiological taking of charge of patients is detailed as well as the prevention campaign.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Knowledge and attitude assessment of Quebec daycare workers and parents regarding HIV/AIDS and hepatitis B.

ISSUES: Cases of discrimination occur in Quebec daycares towards HIV-positive children as well as HIV-negative children born to seropositive parents. OBJECTIVES: Offer three-hour information sessions on bloodborne diseases, specifically HIV and hepatitis B, universal precautions, as well as legal, ethical and psychosocial aspects of HIV/AIDS to: 1) ensure that daycare workers have basic medical information on transmission of HIV and other bloodborne infections, 2) review basic hygiene including universal precautions, 3) link daycares to HIV/AIDS resources in their communities, and 4) facilitate the development of pro-active daycare policies for the integration of HIV-positive children. RESULTS: In total, 108 information sessions were given, in which 349 daycares participated. Results show an important difference in terms of knowledge and attitudes of the participants. Of the daycares which participated in the information sessions, 37% have developed their own pro-active policy.

Adult↗